Effects of chronic renal failure and growth hormone on serum levels of insulin-like growth factor-binding protein-4 (IGFBP-4) and IGFBP-5 in children: A report of the southwest pediatric nephrology study group

Children with chronic renal failure (CRF) have high serum levels of insulin -like growth factor (IGF)-binding protein-1 (IGFBP-1), -2, and -6. The exce ss IGFBP-2 and -1 may play a role in the growth failure of CRF children by sequestering IGF peptides. In contrast, IGFBP-3 levels rise with GH treatme nt of CRF children, suggesting a role for IGFBP-3 in their accelerated grow th. The present studies used sensitive and specific antisera to characteriz e levels and forms of IGFBP-4 and -5 in serum from CRF children. By RIA, th e mean baseline serum level of IGFBP-4 was high in CRF children compared to that in normal children, but the IGFBP-4 level in CRF serum did not correl ate with height SD score; by immunoblot, high CRF levels were associated wi th increases in both intact and fragmented IGFBP-4. Mean RIA levels of IGFB P-5 were comparable in sera from CRF and normal children. Treating CRF chil dren with GH for 12 months increased serum IGFBP-4 levels by 26% and IGFBP- 5 levels by 49%, as determined by RIA; levels of IGFBP-5, but not IGFBP-4, correlated significantly with serum levels of IGF-I, IGF-II, IGFBP-3, and a cid-labile subunit and with growth rate in these GH-treated children. In su mmary, IGFBP-4 levels are high in serum of CRF children, and GH increases s erum levels of IGFBP-4 and IGFBP-5 in these children. The data suggest a ro le for IGFBP-5 in the accelerated growth of GH-treated CRF children, perhap s as part of a ternary complex with acid-labile subunit and IGFs. Additiona l studies on the relationship between intact IGFBP-4 levels and growth are needed to determine what role IGFBP-4 plays in the linear growth process in vivo.